During his confirmation in the Senate for the UN post, most of the tough questions asked of Negroponte related to his activities while US ambassador to Honduras. Honduras was ruled at the time by a military dictatorship under the command of General Gustavo Alvarez Martinez. Honduras was in a geopolitical situation that made it a top priority of the United States at the time, being bordered by Nicaragua, where the leftist Sandinistas had taken over, and El Salvador and Guatemala, where leftist guerrillas had strong organizations and support. The US, beginning in the Carter administration, not Reagan's, identified Honduras as the place where we would make our stand against communism in Central America, by maintaining the right wing government there and using its military to provide aid to the Contras in Nicaragua. There is strong evidence that Negroponte knew about and covered up human rights violations by the US trained and supported Honduran military, due to the strategic importance of Honduras to the US.

Jack Binns, Jimmy Carter's ambassador to Honduras, remained in that post under President Reagan until the summer of 1981. On his watch, Battalion 316, a secret intelligence unit of the Honduran army, received training and logistic support from the CIA, and later received specialized training at the School of the Americas. On Negroponte's watch, while US military aid to Honduras increased from $4 million to $77 million, the real brutality began.

In 1981, Binns, who had been reporting human rights violations, was called to Washington and told to make his reports through "back channels," which don't officially exist, in order to prevent leaks. In the briefing book that Binns left for Negroponte in 1981, he detailed an "escalation of human rights issues." In 1982, the Honduran press ran 318 stories about murders and kidnappings committed by the Honduran military. Rick Chidester, an official who served under Negroponte in 1982, says he was ordered to remove any mention of torture and executions from the draft of his report on the human rights situation in Honduras. According to a four part series in the Baltimore Sun in 1995, Battalion 316 used "shock and suffocation devices in interrogations. Prisoners often were kept naked and, when no longer useful, killed and buried in unmarked graves.” The Sun series also documents the fact that underlings in the US embassy at the time reported cases of torture and human rights violations to Negroponte and to Washington. But these reports were never included in the final drafts of annual human rights reports to Congress, which influenced US funding decisions. In fact, Negroponte was confident enough to state in these reports that it was "simply untrue to state that death squads have made their appearance in Honduras," that there were "no political prisoners in Honduras" and that the "Honduran government neither condones nor knowingly permits killings of a political or nonpolitical nature." A 1997 CIA inquiry found that "the embassy was aware of Honduran military involvement in death squad activities and that inadequacies and inconsistencies in reporting obscured the scope of human rights abuses in the country."

Negroponte, although he was never a defendant in the Iran-Contra hearings and was not challenged on his activities in Honduras during subsequent Senate hearings for ambassadorial posts (until this year), has had occasion to speak in his defense several times.

In a 1997 interview with CNN for their Cold War series, he said this: " Some of these regimes, to the outside observer, may not have been as savory as Americans would have liked; they may have been dictators, or likely to become dictators, when you would have been wanting to support democracy in the area. But with the turmoil that was there, it was perhaps not possible to do that."

And in his 2001 Senate confirmation hearing, he did not deny that human rights violation took place in Honduras on his watch, only that he had any knowledge of violations.